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* To whom correspondence should be addressed. E-mail: renkeli{at}uhnres.utoronto.ca.
Background: The functional benefit of cell transplantation after a myocardial infarction is diminished by early cell losses. Insulin-like growth factor-1 (IGF-1) enhances cell proliferation and survival. We hypothesized that IGF-1 transfected smooth muscle cells (SMC) would enhance cell survival and improve engraftment after cell transplantation. Methods and Results: IGF-1 gene was transfected into male SMC and compared to SMC transfected with a plasmid vector (vector control) and non-transfected SMC (cell control). In Vitro Studies: IGF-1 mRNA (n=10/group) and protein levels (n=6/group) were higher (p<0.05 for all groups) at 3, 7 and 14 days compared to controls. Vascular endothelial growth factor (VEGF) was also increased in parallel to enhanced IGF-1 expression. IGF-1 transfected cells demonstrated greater cell proliferation, stimulated angiogenesis and decreased caspase-3 activity after simulated ischemia and reperfusion (p<0.05 for all groups compared to vector or cell controls). In Vivo Studies: A uniform left ventricular injury was produced in female rats using a cryoprobe. Three weeks later, 2x106 from 3 groups were implanted into the scar. One week later, IGF-1 transfected SMCs increased myocardial IGF-1 and VEGF levels, increased Bcl2 expression, limited cell apoptosis, and enhanced vessel formation in the myocardial scar as compared to the two control groups (p<0.05 for all groups). The proportion of SMC surviving in the implanted region was greater (p<0.05) in the IGF-1 transfected group than in the vector or cell controls. Conclusions: Gene enhancement with IGF-1 improved donor cell proliferation, survival, and engraftment after cell transplantation, perhaps mediated by enhanced angiogenesis and reduced apoptosis.
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